Histology Atlas of the Developing Prenatal and Postnatal Mouse Central Nervous System, with Emphasis on Prenatal Days E7.5 to E18.5

Abstract

Evaluation of the central nervous system (CNS) in the developing mouse presents unique challenges given the complexity of ontogenesis, marked structural reorganization over very short distances in three dimensions each hour, and numerous developmental events susceptible to genetic and environmental influences. Developmental defects affecting the brain and spinal cord arise frequently both in utero and perinatally as spontaneous events, following teratogen exposure, and as sequelae to induced mutations, and thus are a common factor in embryonic and perinatal lethality in many mouse models. Knowledge of normal organ and cellular architecture and differentiation throughout the mouse’s lifespan is crucial to identify and characterize neurodevelopmental lesions. By providing a well-illustrated overview summarizing major events of normal in utero and perinatal mouse CNS development with examples of common developmental abnormalities, this annotated, color atlas can be used to identify normal structure and histology when phenotyping genetically engineered mice (GEM) and will enhance efforts to describe and interpret brain and spinal cord malformations as causes of mouse embryonic and perinatal lethal phenotypes. The schematics and images in this atlas illustrate major developmental events during gestation from embryonic day (E) 7.5 to E18.5 and after birth from postnatal day (P)1 to P21.

Resolving cell cycle speed in one snapshot with a live-cell fluorescent reporter

“…The proliferative behavior revealed by H2B-FT confirms known developmental timelines (Chen et al, 2017) and again is consistent with the pattern of EdU staining ( Figure 6C, bottom). Even for cells that exit cell cycle upon differentiation, the gradually decreasing blue/red ratio shouldup to a point -report relative time elapsed since their last division.…”

“…Past this point, cells plateau in their ability to become redder over time, reaching the resolution limit of the H2B-FT reporter. This is exemplified in the homogeneously red-shifted thalamus ( Figure 6E), where new neuron production peaks at E14 but trails off by E17 (Chen et al, 2017). Therefore, H2B-FT nuclei quantified in situ readily reveals the distribution of relative cell cycle lengths in a given tissue ( Figure 6F), similar to what we have shown using flow cytometry.…”

Mitochondrial and glycolytic remodeling during nascent neural differentiation of human pluripotent stem cells

“…The earliest neural developments of the implanted mouse embryo, starting at E7 (Chen et al, 2017), take place at physiological (<5%) oxygen concentrations (Genbacev et al, 1997;Caniggia et al, 2000). To determine whether physiological oxygen would alter hPSC metabolism or differentiation kinetics throughout NPC induction, we induced hPSCs adapted for over ten passages at 5% and 20% oxygen to differentiate to NPCs at the same oxygen level.…”

“…The hPSC-derived NPC state corresponds to embryonic day (E) 8.5 in the developing mouse egg cylinder when neural crest development takes place (Chambers et al, 2009;Chen et al, 2017). From implantation at E5, through neural tube, neural crest, and brain vesicle development at E7-E9.5, mouse embryo metabolism is almost exclusively glycolytic (Clough and Whittingham, 1983).…”

Loss of Ing3 Expression Results in Growth Retardation and Embryonic Death

“…The results clearly show the developmental failure upon loss of ING3 expression. µ CT analysis revealed a general delay in growth in homozygous embryos with major growth restriction in the closing of the brain buds and further formation of the three primary brain vesicles (prosencephalon, mesencephalon, and rhombencephalon) seen in heterozygous and wild type embryos at E10.5 [34]. The brain is closed at Theiler stage 14 (E9.0, 13-20 somites) in normal development before limb buds start to appear [32].…”